The Rho-specific GEF Lfc Interacts With Neurabin and Spinophilin to Regulate Dendritic Spine Morphology

Neuron. 2005 Jul 7;47(1):85-100. doi: 10.1016/j.neuron.2005.05.013.

Abstract

Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. A yeast two-hybrid analysis using the coiled-coil domain of neurabin revealed an interaction with Lfc, a Rho GEF. Lfc was highly expressed in brain, where it interacted with either neurabin or spinophilin. In neurons, Lfc was largely found in the shaft of dendrites in association with microtubules but translocated to spines upon neuronal stimulation. Moreover, expression of Lfc resulted in reduction in spine length and size. Both the translocation and the effect on spine morphology depended on the coiled-coil domain of Lfc. Coexpression of neurabin or spinophilin with Lfc resulted in their clustering together with F-actin, a process that depended on Rho activity. Thus, interaction between Lfc and neurabin/spinophilin selectively regulates Rho-dependent organization of F-actin in spines and is a link between the microtubule and F-actin cytoskeletons in dendrites.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Actins / physiology
  • Animals
  • Brain Chemistry
  • Carbocyanines
  • Coloring Agents
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • Dendrites / metabolism
  • Dendrites / physiology
  • Dendrites / ultrastructure*
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Immunohistochemistry
  • Microfilament Proteins / metabolism
  • Microfilament Proteins / physiology*
  • Microscopy, Confocal
  • Microtubules / drug effects
  • Microtubules / ultrastructure
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Phalloidine
  • Rats
  • Transfection

Substances

  • Actins
  • Carbocyanines
  • Coloring Agents
  • DNA, Complementary
  • Guanine Nucleotide Exchange Factors
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • neurabin
  • Guanosine Diphosphate
  • Phalloidine
  • 3,3'-dioctadecylindocarbocyanine
  • Guanosine Triphosphate